Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods, and Applications

Abstract

The traditional Chinese medicine (TCM), which has thousands of years of clinical application among China and other Asian countries, is the pioneer of the “multicomponent-multitarget” and network pharmacology. Although there is no doubt of the efficacy, it is difficult to elucidate convincing underlying mechanism of TCM due to its complex composition and unclear pharmacology. The use of ligand-protein networks has been gaining significant value in the history of drug discovery while its application in TCM is still in its early stage. This paper firstly surveys TCM databases for virtual screening that have been greatly expanded in size and data diversity in recent years. On that basis, different screening methods and strategies for identifying active ingredients and targets of TCM are outlined based on the amount of network information available, both on sides of ligand bioactivity and the protein structures. Furthermore, applications of successful in silico target identification attempts are discussed in detail along with experiments in exploring the ligand-protein networks of TCM. Finally, it will be concluded that the prospective application of ligand-protein networks can be used not only to predict protein targets of a small molecule, but also to explore the mode of action of TCM.

Network Pharmacology to Unveil the Biological Basis of Health-Strengthening Herbal Medicine in Cancer Treatment

“…An increasing amount of evidence indicates that TCM may exert therapeutic effects by targeting a variety of biomolecules [ 22 ]. However, due to the complexity of the ingredients and the limitations in the application of experimental methods, the targets of many TCM compounds are still unclear [ 23 ]. It has been proposed that TCM formulae and herbs impact the network of targets in complex diseases, such as cancer [ 24 , 25 , 26 , 27 ], and researchers may investigate the systemic effects of drugs on biological networks.…”

Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective

“…While most of the researches focus on virtual screening of the databases by various computational tools like chemical similarity search, docking, and molecular dynamics [31–34], drug-likeness analysis was also applied to the TCM databases in order to investigate the pharmaceutical potential of natural compounds. For example, Shen et al published a series of papers on the topic of drug-likeness analysis of traditional Chinese medicines by comparing the molecular properties and scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines.…”

Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes

“…The mixture of compounds in the formula works through the therapeutic principle Jun-Chen-Zuo-Shi , by maximizing the therapeutic effects and minimizing the side effects [ 1 , 15 , 16 ]. Based on the healing/pharmacological properties and constituents of each medicine, the Jun (emperor) component is the principal phytocomplex targeting the major symptom of the disease.…”